Biomedical subjects

Philippe Siaud

Publications and source records attributed to Philippe Siaud.

4 recordsLinked to original sources

PubMed2006

Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.

OBJECTIVE: We asked whether blockade of voltage-gated K+ channel Kv1.1, whose altered axonal localization during myelin insult and remyelination may disturb nerve conduction, treats experimental autoimmune encephalomyelitis (EAE). METHODS: Electrophysiological, cell proliferation, cytokine secretion, immunohistochemical, clinical, brain magnetic resonance imaging, and spectroscopy studies assessed the effects of a selective blocker of Kv1.1, BgK-F6A, on neurons and immune cells in vitro and on EAE-induced neurological deficits and brain lesions in Lewis rats. RESULTS: BgK-F6A increased the frequency of miniature excitatory postsynaptic currents in neurons and did not affect T-cell activation. EAE was characterized by ventriculomegaly, decreased apparent diffusion coefficient, and decreased (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Reduced apparent diffusion coefficient and impaired energy metabolism indicate astrocytic edema. Intracerebroventricularly BgK-F6A-treated rats showed attenuated clinical EAE with unexpectedly reduced ventriculomegaly and preserved apparent diffusion coefficient values and (phosphocreatine + beta-adenosine triphosphate)/inorganic phosphate ratio. Thus, under BgK-F6A treatment, brain damage was dramatically reduced and energy metabolism maintained. INTERPRETATION: Kv1.1 blockade may target neurons and astrocytes, and modulate neuronal activity and neural cell volume, which may partly account for the attenuation of the neurological deficits. We propose that Kv1.1 blockade has a broad therapeutic potential in neuroinflammatory diseases (multiple sclerosis, stroke, and trauma).

Animals↗

PubMed2006

Enhanced cochlear acoustic sensitivity and susceptibility to endotoxin are induced by adrenalectomy and reversed by corticosterone supplementation in rat.

Glucocorticoid receptors are widely distributed in the cochlea but their role remains poorly known. Previous studies provided contradictory reports on a possible cochlear acoustic hypersensitivity induced by adrenal insufficiency, while several experiments agree on a significant action of glucocorticoid receptors in adverse conditions such as acoustic trauma and restraint stress. The present experiments confirmed a cochlear acoustic hypersensitivity induced by adrenalectomy and reversed by corticosterone supplementation. These observations point to a significant role of corticosteroids in basal cochlear functioning. The glucocorticoids are known to be essential for limiting and resolving inflammatory processes. The endotoxin Escherichia coli lipopolysaccharide is widely used to induce inflammatory reactions. However, in various organs several toxic processes of this endotoxin are not influenced by glucocorticoids. From previous experiments on the cochlea there is no evidence that glucocorticoids are an essential factor against endotoxin cochlear toxicity. In the present experiments it was found that adrenalectomy greatly increased the cochlear susceptibility to endotoxin; the effect was reversed by providing corticosterone supplementation. This shows the essential role of corticosterone in this cochlear inflammation model. In previous studies local administration (at the cochlear base) of endotoxin was used and losses of cochlear acoustic sensitivity were found predominantly at high frequencies; in contrast, the systemic injection used in this study produced a cochlear loss of acoustic sensitivity at all frequencies, indicating a uniform cochlear sensitivity to the toxic effects of endotoxin.

Acoustic Stimulation↗

PubMed2004

Hexachlorobenzene, a dioxin-like compound, disrupts auditory function in rat.

Hexachlorobenzene (HCB) is a dioxin-like compound widely distributed in the environment. In this study, we investigated the effects of HCB on the cochlea. Conscious free-moving rats were given HCB per os daily for 4 weeks at doses of 0.16, 4 or 16 mg/kg in olive oil, whereas the control group received olive oil only. The effects of HCB were evaluated at various time intervals, by measuring auditory nerve acoustic thresholds and plasma thyroid hormone concentration by radioimmunoassay. Histological evaluation involved surface preparation and scanning electron microscopy observations of cochlear hair cells. At a dose of 0.16 mg/kg, HCB induced no loss of acoustic sensitivity, whereas at 4 mg/kg, it induced cochlear sensitivity deficits at the mid-frequencies (2-16 kHz) with complete recovery once treatment was stopped. At a dose of 16 mg/kg, permanent threshold shifts were observed at all frequencies tested (from 1 to 32 kHz). Morphological studies showed no cochlear hair cell loss or alteration of stereocilia. HCB treatment reduced circulating thyroxine concentrations. Thyroidectomy had no effect on cochlear sensitivity in control animals. Thus, HCB is a potent oto-toxicant, and its ototoxicity may be independent of its thyroidal effects.

Animals↗

PubMed2002

Testicular activity is restored by melatonin replacement after suprachiasmatic nucleus lesion or superior cervical ganglionectomy in mink.

Subcutaneous melatonin implants were inserted in mink subjected to natural (autumn) or experimental gonadostimulatory short-days (4L:20D), after lesion of the suprachiasmatic nucleus (SCNx) or after superior cervical ganglionectomy (SCGx). Gonad stimulation was assessed by measuring testicular volume and plasma testosterone level. In SCNx and SCGx animals, all measurements were indicative of sexual quiescence. In contrast, both SCNx and SCGx animals with melatonin, maintained in natural or experimental gonadostimulating short-days, showed an increase in testicular activity 2 months after melatonin implantation. Thus, melatonin (and pineal activity) is a prerequisite for the photoperiodic stimulation of reproductive activity, and the SCN is not necessarily the target site for melatonin action on the renewal of reproduction in the mink.

Animals↗